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- Title
Tracking longitudinal genetic changes of circulating tumor DNA (ctDNA) in advanced Lung adenocarcinoma treated with chemotherapy.
- Authors
Han, Xiaohong; Han, Ying; Tan, Qiaoyun; Huang, Yu; Yang, Jianliang; Yang, Sheng; He, Xiaohui; Zhou, Shengyu; Song, Yan; Pi, Jinping; Zuo, Lijie; Yao, Jiarui; Wu, Di; Zhang, Zhishang; Shi, Yuankai
- Abstract
<bold>Introduction: </bold>Pemetrexed combined with platinum complexes can be used as first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC), however, the efficacy and safety is varying from individuals. There is a need to better understand the genetic variations associated with platinum response.<bold>Materials and Methods: </bold>We performed next-generation sequencing (NGS) based on BGI Oseq-ctDNA panel to analyze 98 longitudinal plasma samples from 32 lung adenocarcinoma patients during platinum-based chemotherapy, and a bioinformatic pipeline was developed to detect point mutations.<bold>Results: </bold>We found that mutation burden was decreased after chemotherapy, which reflected chemotherapy sensitivity, especially the frequency of C>G and C>A substitutions. Moreover, neoplastic cells carrying a specific set of somatic mutations, such as EGFR(L858R), KRAS (p.G12C) were obviously correlated with platinum treatment. In addition, the MAPK pathway was found to have a pivotal role in NSCLC and platinum based response. Finally, we found that smokers benefit less from platinum-based chemotherapy.<bold>Conclusions: </bold>Collectively, this work described the dynamic changes of ctDNA mutation status during platinum-based treatment, which may contribute to advanced lung adenocarcinoma patients stratification and precision treatment.
- Subjects
GENETIC mutation; CIRCULATING tumor DNA; NON-small-cell lung carcinoma; ADENOCARCINOMA; LUNGS; CANCER chemotherapy
- Publication
Journal of Translational Medicine, 2019, Vol 17, Issue 1, pN.PAG
- ISSN
1479-5876
- Publication type
journal article
- DOI
10.1186/s12967-019-2087-9